The growth of neurodegenerative diseases such as dementia leads to problems
for an increasing number of affected patients and their families as well as
for the health economic system. Early detection of associated risk factors and
the search for novel preventive strategies is thus of major importance. Within
the scope of three studies, this thesis explored relationships between
behavioral, structural and neurophysiological brain parameters and blood
markers in a cohort of healthy older people to provide support for future
prevention strategies. The first study elucidated relationships between
structural and neurophysiological parameters of gray and white matter in 30
subjects. Previous studies demonstrated reduced resting motor threshold (rMT)
in patients with Alzheimer’s disease. In the present study, regression
analyses indicated that cortical excitability was best predicted by cortical
thickness and coil-to-cortex distance. Moreover, lower rMT was associated with
reduced learning ability. The results suggest that lower rMT may be a
parameter to identify a potential risk for cognitive decline within this
cohort. The second study investigated associations between peripheral glucose
metabolism (HbA1c, fasting glucose), memory performance, and volume as well as
microstructure of the hippocampus (HC). 141 subjects underwent
neuropsychological testings, 3 Tesla MRI and donated fasting blood samples.
Regression models indicated a strong association between higher HbA1c levels
and reduced memory performance. Mediation models revealed that the effects of
HbA1c on memory are partially mediated by structural HC parameters. This
indicates a negative influence of elevated glucose levels even in the absence
of pathological values. Future interventions, aiming at lowering blood sugar
levels, might be initiated. The third study tested whether 26 weeks of omega-3
fatty acid (o-3 FA) supplementation (2.2 g/day) would benefit cognition and
brain structure. 65 subjects (o-3 FA vs. placebo) underwent neuropsychological
testings, MRI, collection of blood samples and measurement of carotid intima-
media thickness (CIMT). A significant increase in omega-3-index (percentage of
o-3 FA in membranes of erythrocytes) and executive functions was found in the
o3-FA group. Longitudinal MRI analyses revealed volume increases (prefrontal
cortex, left HC) as well as regional improvements of left-hemispheric white
matter integrity within the intervention group. Moreover, o-3 FA lowered
global brain atrophy and CIMT in females. This data suggests that o-3 FA may
benefit executive functioning, corresponding brain areas and markers of
atherosclerosis. Based on these findings, novel prevention strategies might be
developed in the future.